Separase

A cysteine protease responsible for triggering anaphase by hydrolysing cohesin

Clonal Evolution and Blast Crisis Correlate with Enhanced Proteolytic Activity of Separase in BCR-ABL b3a2 Fusion Type CML under Imatinib Therapy.

Clonal Evolution and Blast Crisis Correlate with Enhanced Proteolytic Activity of Separase in BCR-ABL b3a2 Fusion Type CML under Imatinib Therapy.

Unbalanced (major route) additional cytogenetic aberrations (ACA) in the diagnosis of chronic myeloid leukemia (CML) showed an increase in the risk of progression and shorter survival. In addition, the emerging ACA under imatinib treatment and clonal evolution regarded acceleration features and determine treatment failure in accordance with the European LeukemiaNet (ELN) recommendation.

On the basis of 1151 patients with chronic phase Philadelphia chromosome positive CML random-IV study, we examine recent events, ACA arising under imatinib treatment in connection with p210BCR-ABL breakpoint variants b2a2 and b3a2. We found the ACA preferential acquisition is not balanced in patients with vs b2a2 b3a2 fusion type (ratio: 6.3 vs. 1.6, p = 0.0246) concurring quickly advanced to the blast crisis for b3a2 patients (p = 0.0124).

ESPL1 / Separase, a cysteine ​​endopeptidase, is a key player in chromosome segregation during mitosis. Separase excess and / or hyperactivity have been reported from a variety of cancers and causes defective mitotic spindle, the chromosomes missegregation and aneuploidy. We investigated the influence of p210BCR-ABL breakpoint variants and treatment of imatinib on expression and proteolytic activity of Separase measured by specific fluorogenic assay in CML cell lines (b2a2: KCL-22, BV-173; b3a2: K562, LAMA-84). Despite the decline in protein content Separase up to 5.4-fold increase from Separase activity under imatinib treatment was observed exclusively in b3a2 but not in cell lines b2a2.

Mimic the effect of imatinib on BV-173 and LAMA-84 cells with silencing ESPL1 Separase stimulated proteolytic activity in cell lines of both b3a2 and b2a2. Our data indicate the presence of a feedback mechanism-related types of post- translational fusion Separase stimulates proteolytic activity after therapy-induced decrease in protein levels Separase. This can make b3a2 CML cells more susceptible to aneuploidy and clonal evolution from a common ancestor b2a2 and therefore can explain the results of cytogenetic patients with CML.

Clonal Evolution and Blast Crisis Correlate with Enhanced Proteolytic Activity of Separase in BCR-ABL b3a2 Fusion Type CML under Imatinib Therapy.
Clonal Evolution and Blast Crisis Correlate with Enhanced Proteolytic Activity of Separase in BCR-ABL b3a2 Fusion Type CML under Imatinib Therapy.

Separase Cleaves N-Tail of CENP-A CPAR Related Protein-1 in Meiosis I Metaphase-Anaphase transition in C. elegans.

Epigenetically defined centromere in most eukaryotes by the presence of centromeric chromatin containing histone H3 variant CENP-A. Most species have a single gene that encodes a centromeric histone variant while C. elegans has two: HCP-3 (also known as CeCENP-A) and CPAR-1. Before the replacement RNAi experiments showed that the HCP-3 is a functional isoform dominant, consistent with CPAR-1 does not become detectable in the embryo.

GFP :: CPAR-1 loaded onto meiotic chromosomes in diakinesis and enriched bivalents until meiosis I. Here we show that the CPAR-1 :: GFP signal loss of chromosome segregation precisely coincide with the homologous during anaphase I. The loss of GFP:: CPAR-1 signal reflects the proteolytic cleavage between GFP and histone fold of CPAR-1, as CPAR-1 :: GFP, where GFP fused to the C-terminus of CPAR-1, showed no GFP signal loss.

A focus of the candidates involved separase screen, proteases which initiate anaphase by splitting kleisin subunit of cohesin, in reaction to this division. Examination of the N-terminal tail sequence CPAR-1 expressing separase cleavage site and a mutation of the residues alleged signatures on this site removed cleavage reaction, as visualized by the retention of CPAR-1 :: GFP signal in separating homologous chromosomes in metaphase-anaphase transition of meiosis I.

Separase (phospho Ser801) Polyclonal Antibody

ABP50519-02ml 0.2ml
EUR 496.8
Description: A polyclonal antibody for detection of Separase phospho Ser801) from Human, Mouse. This Separase phospho Ser801) antibody is for WB , IHC-P, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from human Separase around the phosphorylation site of S801

Separase (phospho Ser801) Polyclonal Antibody

ES1518-100ul 100ul
EUR 334.8
Description: A Rabbit Polyclonal antibody against Separase (phospho Ser801) from Human/Mouse. This antibody is tested and validated for WB, ELISA, IHC, IF, WB, ELISA

Separase (phospho Ser801) Polyclonal Antibody

ES1518-50ul 50ul
EUR 248.4
Description: A Rabbit Polyclonal antibody against Separase (phospho Ser801) from Human/Mouse. This antibody is tested and validated for WB, ELISA, IHC, IF, WB, ELISA

Phospho-SEPARASE (Ser801) Colorimetric Cell-Based ELISA Kit (OKAG01525)

OKAG01525 2 x 96 Wells
EUR 888
Description: Description of target: ;Species reactivity: Human: S801, Mouse: S1189;Application: ELISA;Assay info: Assay Type: Cell-Based
Subtype: Phospho
Detection Method: Colorimetric 450 nm;Sensitivity:

Separase (Phospho-Ser801) Polyclonal Antibody

12353-100ul 100ul
EUR 302.4

Separase (Phospho-Ser801) Polyclonal Antibody

12353-50ul 50ul
EUR 224.4

Phospho-MEK1/2 (Ser218+Ser222/Ser222+Ser226) Antibody

AF8035 200ul
EUR 540

Phospho-RSK1/2/3/4 (Ser221/Ser227/Ser218/Ser232) Antibody

AF3810 100ul
EUR 540

Phospho-RSK1/2/3/4 (Ser221/Ser227/Ser218/Ser232) Antibody

DF8743 200ul
EUR 420

Phospho-STAT5 (Ser725/Ser730)[Ser726/Ser731] Antibody

AF3304 200ul
EUR 420

Phospho-PAK1 /PAK2 (Ser199/Ser204, Ser192/Ser197) Antibody

AF2380 200ul
EUR 420

Phospho-PAK1/2/3 (Ser144+Ser141+Ser139) Antibody

DF2948 200ul
EUR 420

Phospho-PAK1/2/3 (Ser144+Ser141+Ser139) Blocking Peptide

DF2948-BP 1mg
EUR 234

PKC mu antibody (Ser738+Ser742)

70R-31523 100 ug
EUR 392.4
Description: Rabbit polyclonal PKC mu antibody (Ser738+Ser742)

Phospho-CD45 (Ser1007)[Ser1009] Antibody

AF3127 200ul
EUR 420

MDM2 antibody (Ser186+Ser188)

70R-36311 100 ug
EUR 392.4
Description: Rabbit polyclonal MDM2 antibody (Ser186+Ser188)

PAK5/6 antibody (Ser602/Ser560)

70R-34560 100 ug
EUR 392.4
Description: Rabbit polyclonal PAK5/6 antibody (Ser602/Ser560)

rpS6 antibody (Ser235+Ser236)

70R-34574 100 ug
EUR 392.4
Description: Rabbit polyclonal rpS6 antibody (Ser235+Ser236)

AMPK antibody (Ser485/Ser491)

70R-35208 100 ug
EUR 392.4
Description: Purified Rabbit polyclonal AMPK antibody (Ser485/Ser491)

Phospho- PAK1 (Ser199/204) /PAK2 (Ser192/197) Antibody

ABF3691 100 ug
EUR 525.6

ADRB2 antibody (Ser355+Ser356)

70R-33353 100 ug
EUR 392.4
Description: Rabbit polyclonal ADRB2 antibody (Ser355+Ser356)

AMPK1 antibody (Ser485/Ser491)

70R-37249 100 ug
EUR 418.8
Description: Rabbit Polyclonal AMPK1 antibody (Ser485/Ser491)

NFAT3 antibody (Ser168+Ser170)

70R-34549 100 ug
EUR 392.4
Description: Rabbit polyclonal NFAT3 antibody (Ser168+Ser170)

PPP1R2 antibody (Ser120+Ser121)

70R-36672 100 ug
EUR 392.4
Description: Rabbit Polyclonal PPP1R2 antibody (Ser120+Ser121)

FOXO1A antibody (Ser322+Ser325)

70R-35267 100 ug
EUR 392.4
Description: Purified Rabbit polyclonal FOXO1A antibody (Ser322+Ser325)

Phospho-Beclin 1 (Ser90/Ser93/Ser96) Antibody

AF7386 200ul
EUR 540

Phospho-AR (Ser650)[Ser651] Antibody

AF3137 200ul
EUR 420

Phospho- Sox2 (Ser250/Ser251) Antibody

ABF3753 100 ug
EUR 525.6

MEK1/2 (Phospho- Ser217+ Ser221) Antibody

ABF8035 100 ug
EUR 525.6

EIF5 (Phospho- Ser389+ Ser390) Antibody

ABF8473 100 ug
EUR 525.6

Phospho-Rel (Ser492/Ser460) Antibody

AF8126 200ul
EUR 540

Phospho-Tau (Ser717/Ser400) Antibody

AF8129 200ul
EUR 540

Phospho-HSL (Ser563)[Ser853] Antibody

AF2350 200ul
EUR 420

Phospho-MFF (Ser172/Ser146) Antibody

AF2365 200ul
EUR 420

Phospho-p63 (Ser160/Ser162) Antibody

AF2379 200ul
EUR 420

Phospho-Tau (Ser199)[Ser516] Antibody

AF2418 200ul
EUR 420

Phospho-Tau (Ser202)[Ser519] Antibody

AF2419 200ul
EUR 420

Phospho-Tau (Ser416)[Ser733] Antibody

AF2420 200ul
EUR 420

Phospho-Tau (Ser356)[Ser673] Antibody

AF3143 200ul
EUR 420

Phospho-Tau (Ser404)[Ser721] Antibody

AF3144 200ul
EUR 420

Phospho-Tau (Ser422)[Ser739] Antibody

AF3145 200ul
EUR 420

Phospho-Tau (Ser262)[Ser579] Antibody

AF3151 200ul
EUR 420

Phospho-HSL (Ser855/Ser554) Antibody

AF3402 200ul
EUR 420

Phospho-BAD (Ser155)[Ser118] Antibody

AF3471 200ul
EUR 420

Phospho-Tau (Ser202/Ser519) Antibody

AF3947 100ul
EUR 540

Smad1/5/9 (Phospho- Ser463+ Ser465) Antibody

ABF8313 100 ug
EUR 525.6

Smad2 (Phospho- Ser465+ Ser467) Antibody

ABF8314 100 ug
EUR 525.6

Smad3 (Phospho- Ser423+ Ser425) Antibody

ABF8315 100 ug
EUR 525.6

MYPT1/2 (Phospho- Ser668/Ser618) Antibody

ABF8447 100 ug
EUR 525.6

Smad1/9 (Phospho- Ser463/Ser465) Antibody

ABF8454 100 ug
EUR 525.6

Phospho-PAK1 (Ser199/204)/PAK2 (Ser192/197) Blocking Peptide

AF2380-BP 1mg
EUR 234

Phospho-EZH2 (Ser363/Ser366) Antibody

AF7401 200ul
EUR 540

Phospho-SOX2 (Ser249/Ser250) Antibody

AF7450 200ul
EUR 540

Phospho-MEK1/2 (Ser212/Ser216) Antibody

AF8165 200ul
EUR 540

Phospho-KSR1 (Ser392)[Ser460] Antibody

AF2358 200ul
EUR 420

Phospho-MKP1/2 (Ser296/Ser318) Antibody

AF3243 200ul
EUR 420

Phospho-MEK1/2 (Ser217)[Ser218] Antibody

AF3384 200ul
EUR 420

Phospho-MEK1/2 (Ser221)[Ser222] Antibody

AF3385 200ul
EUR 420

Phospho-PAK5/6 (Ser602/Ser560) Antibody

AF3522 100ul
EUR 540

Phospho-GBF1 (Ser292/Ser297) Antibody

AF3565 100ul
EUR 540

Phospho-n-Myc (Ser261/Ser263) Antibody

AF3750 100ul
EUR 540

Phospho-ZIP7 (Ser275/Ser276) Antibody

AF3866 100ul
EUR 540

Phospho-n-Myc (Ser261/Ser263) Antibody

AF3881 100ul
EUR 540

Phospho-IRF7 (Ser471/Ser472) Antibody

AF3885 100ul
EUR 540

Phospho-IRF-7 (Ser437/Ser438) Antibody

AF3886 100ul
EUR 540

Phospho-MDM2 (Ser186/Ser188) Antibody

AF3964 100ul
EUR 540

Phospho-EIF5 (Ser389+Ser390) Antibody

AF8473 200ul
EUR 540

Phospho-TRF2 (Ser323)[Ser365] Antibody

AF8519 200ul
EUR 540

Phospho-ULK1 (Ser757)[Ser758] Antibody

AF4387 200ul
EUR 540

Phospho-IRS1 (Ser318)[Ser323] Antibody

AF4422 200ul
EUR 540

Phospho-ULK1 (Ser555)[Ser556] Antibody

AF7148 200ul
EUR 540

Phospho-MDM2 (Ser186/Ser188) Antibody

CSB-PA570037- each
EUR 402
Description: A polyclonal antibody against Phospho-MDM2 (Ser186/Ser188). Recognizes Phospho-MDM2 (Ser186/Ser188) from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IF;IF:1:100-1:200

Phospho-MDM2 (Ser186/Ser188) Antibody

CSB-PA570037-100ul 100ul
EUR 434.4
Description: A polyclonal antibody against Phospho-MDM2 (Ser186/Ser188). Recognizes Phospho-MDM2 (Ser186/Ser188) from Human. This antibody is Unconjugated. Tested in the following application: ELISA, IF;IF:1:100-1:200

INSP3 antibody (Ser1598/1588)

70R-35490 100 ug
EUR 392.4
Description: Purified Rabbit polyclonal INSP3 antibody (Ser1598/1588)

Phospho-CXCR4 (Ser338/Ser339) Antibody

AF7329 200ul
EUR 540

Phospho-NCoA2 (Ser698/Ser699) Antibody

AF7394 200ul
EUR 540

Phospho-LATS1/2 (Ser909/Ser872) Antibody

AF8163 200ul
EUR 540

Phospho-CtBP1/2 (Ser158/Ser164) Antibody

AF8259 200ul
EUR 540

Phospho-Smad1/5/9 (Ser463+Ser465) Antibody

AF8313 200ul
EUR 540

Phospho-Smad2 (Ser465+Ser467) Antibody

AF8314 200ul
EUR 540

Phospho-Smad3 (Ser423+Ser425) Antibody

AF8315 200ul
EUR 540

Phospho-HIF1A (Ser641/Ser643) antibody

AF0062 100ul
EUR 420

Phospho-PKD1/2/3/PKC mu (Ser738+Ser742) Antibody

AF3444 200ul
EUR 420

Phospho-SRPK2 (Ser494/Ser497) Antibody

AF3633 100ul
EUR 540

Phospho-CXCR4 (Ser324/Ser325) Antibody

AF3641 100ul
EUR 540

Phospho-eEF2K (Ser491/Ser492) Antibody

AF3785 100ul
EUR 540

Phospho-TDP43 (Ser409/Ser410) Antibody

AF3832 100ul
EUR 540

Phospho-Smad5 (Ser463/Ser465) Antibody

AF3899 100ul
EUR 540

Phospho-MYPT1/2 (Ser668/Ser618) Antibody

AF8447 200ul
EUR 540

Phospho-Smad1/9 (Ser463/Ser465) Antibody

AF8454 200ul
EUR 540

Phospho-PDHA1/2 (Ser293/Ser291) Antibody

AF8502 200ul
EUR 540

Phospho-Rad17 (Ser635)[Ser646] Antibody

AF4388 200ul
EUR 540

Phospho-OPRM1 (Ser375)[Ser377] Antibody

AF4420 200ul
EUR 540

Phospho-Smad5 (Ser463/Ser465) Antibody

DF2950 200ul
EUR 420

Phospho-CAMKK1/2 (Ser458/Ser495) Antibody

AF8136 200ul
EUR 540

Phospho-DNMT3A (Ser390/Ser393) Antibody

AF3503 100ul
EUR 540

Phospho-FOXO3A (Ser318/Ser321) Antibody

AF3772 100ul
EUR 540

Phospho-MKK3/MKK6 (Ser189/Ser207) Antibody

AF3804 100ul
EUR 540

Phospho-BCKDHA (Ser292/Ser337) Antibody

AF3826 100ul
EUR 540

Phospho-TGFBR2 (Ser225/Ser250) Antibody

AF3954 100ul
EUR 540

Phospho-PPP1R2 (Ser120/Ser121) Antibody

AF3977 100ul
EUR 540

Phospho-IFNAR1 (Ser535/Ser539) Antibody

CSB-PA041971- each
EUR 402
Description: A polyclonal antibody against Phospho-IFNAR1 (Ser535/Ser539). Recognizes Phospho-IFNAR1 (Ser535/Ser539) from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB;WB:1:500-1:1000

Phospho-IFNAR1 (Ser535/Ser539) Antibody

CSB-PA041971-100ul 100ul
EUR 434.4
Description: A polyclonal antibody against Phospho-IFNAR1 (Ser535/Ser539). Recognizes Phospho-IFNAR1 (Ser535/Ser539) from Human. This antibody is Unconjugated. Tested in the following application: ELISA, WB;WB:1:500-1:1000

Phospho-PAK7/PAK6 (Ser602/Ser560) Antibody

CSB-PA285604- each
EUR 402
Description: A polyclonal antibody against Phospho-PAK7/PAK6 (Ser602/Ser560). Recognizes Phospho-PAK7/PAK6 (Ser602/Ser560) from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB;WB:1:500-1:1000

Phospho-PAK7/PAK6 (Ser602/Ser560) Antibody

CSB-PA285604-100ul 100ul
EUR 434.4
Description: A polyclonal antibody against Phospho-PAK7/PAK6 (Ser602/Ser560). Recognizes Phospho-PAK7/PAK6 (Ser602/Ser560) from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB;WB:1:500-1:1000

Phospho-MAP2K1 (Ser217/Ser221) Antibody

CSB-PA297521- each
EUR 402
Description: A polyclonal antibody against Phospho-MAP2K1 (Ser217/Ser221). Recognizes Phospho-MAP2K1 (Ser217/Ser221) from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC;WB:1:500-1:1000, IHC:1:50-1:100

Phospho-MAP2K1 (Ser217/Ser221) Antibody

CSB-PA297521-100ul 100ul
EUR 434.4
Description: A polyclonal antibody against Phospho-MAP2K1 (Ser217/Ser221). Recognizes Phospho-MAP2K1 (Ser217/Ser221) from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC;WB:1:500-1:1000, IHC:1:50-1:100

Phospho-PPP1R2 (Ser120/Ser121) Antibody

CSB-PA960014- each
EUR 402
Description: A polyclonal antibody against Phospho-PPP1R2 (Ser120/Ser121). Recognizes Phospho-PPP1R2 (Ser120/Ser121) from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, IHC;IHC:1:50-1:100

Phospho-PPP1R2 (Ser120/Ser121) Antibody

CSB-PA960014-100ul 100ul
EUR 434.4
Description: A polyclonal antibody against Phospho-PPP1R2 (Ser120/Ser121). Recognizes Phospho-PPP1R2 (Ser120/Ser121) from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, IHC;IHC:1:50-1:100

Phospho-Hsp90 beta (Ser254)[Ser255] Antibody

AF3126 200ul
EUR 420

Phospho-p70 S6 Kinase (Ser411)[Ser434] Antibody

AF3229 200ul
EUR 420

Phospho-p70 S6 Kinase (Ser424)[Ser447] Antibody

AF3230 200ul
EUR 420

Anti-Phospho PKD1/2/3/PKC mu (Ser738+Ser742) Antibody

P30439 100ul
EUR 476.4
Description: Rabbit Polyclonal Phospho PKD1/2/3/PKC mu (Ser738+Ser742) Antibody. Validated in IHC, WB and tested in Human, Mouse, Rat.

Phospho-Tau-Ser198/Ser199/Ser202 Rabbit pAb

AP1096-100ul 100 ul
EUR 460.8

Phospho-Tau-Ser198/Ser199/Ser202 Rabbit pAb

AP1096-200ul 200 ul
EUR 664.8

Phospho-Tau-Ser198/Ser199/Ser202 Rabbit pAb

AP1096-20ul 20 ul
EUR 219.6

Phospho-Tau-Ser198/Ser199/Ser202 Rabbit pAb

AP1096-50ul 50 ul
EUR 318

PAK1/2/3 (Phospho-Ser144+Ser141+Ser139) Antibody

12795-100ul 100ul
EUR 302.4

PAK1/2/3 (Phospho-Ser144+Ser141+Ser139) Antibody

12795-50ul 50ul
EUR 224.4

Phospho-IKK alpha/ beta (Ser180/Ser181) Antibody

AF3013 200ul
EUR 420

Phospho-IKK alpha/ beta (Ser176/Ser177) Antibody

AF3014 200ul
EUR 420

Phospho-Histone H2A.X (Ser139)[Ser140] Antibody

AF3187 200ul
EUR 420

Phospho-RUNX1/RUNX3 (Ser435/Ser397) Antibody

AF3624 100ul
EUR 540

Phospho-IKK alpha/ beta (Ser176/Ser180) Antibody

AF3800 100ul
EUR 540

Phospho-BAD (Ser112)[Ser75] Antibody

AF7427 200ul
EUR 540

Phospho-Bim (Ser44/Ser104) Antibody

AF8248 200ul
EUR 540

Phospho-SRF (Ser99)[Ser103] Antibody

AF3160 200ul
EUR 420

Phospho-BAD (Ser136)[Ser99] Antibody

AF3472 200ul
EUR 420

Phospho-BAD (Ser91/Ser128) Antibody

AF3950 100ul
EUR 540

Phospho-MEK1/2 (Ser217+Ser221) Blocking Peptide

AF8035-BP 1mg
EUR 234

Phospho-EIF5 (Ser389+Ser390) Blocking Peptide

AF8473-BP 1mg
EUR 234

Neither whether or uncleavable CPAR-1 centromere-localized in mitosis and not locally around chromatin, indicating that activity has not been retained in the CPAR centromere-1. Although the function of CPAR-1 and cleavage depends separase that remains to be explained, these efforts reveal new substrate separase and provide in vivo biosensors to monitor activity at the beginning of meiosis I separase anaphase.

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